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MECHANISM OF ACTION

View the Science Behind the Unique Mechanism
of Action of DUPIXENT1,*

View the Science Behind the Unique Mechanism
of Action of DUPIXENT1,*

DUPIXENT TARGETS TWO OF THE KEY AND CENTRAL DRIVERS OF
TYPE 2 INFLAMMATION—IL-4 AND
IL-13 SIGNALING1-3,*

Only DUPIXENT directly inhibits IL-4 and IL-13 signaling1,*

*The mechanism of dupilumab action has not been definitively established.1

DUPIXENT inhibits IL-4 and IL-13 signaling by specifically binding to the IL-4 receptor alpha (IL-4Rα) subunit.1,* Blocking IL-4Rα with DUPIXENT inhibits IL-4– and IL-13–induced inflammatory responses, including mucosal IgE production, and lowers total IgE in the blood of patients with CRSwNP, thereby demonstrating both local and systemic effects of DUPIXENT on these markers of type 2 inflammation in CRSwNP1,8,*:

DUPIXENT targets THE SIGNALING OF both the IL-4 and
IL-13 cytokines, meaning we are targeting these
two major drivers of type 2 inflammation common
to CRSwNP.1-3,*

Nicole Chase, MD, FAAP, FAAAAI, FACAAI

Paid Partner

Allergist/Immunologist, Partner, St. Paul Allergy & Asthma, P.A.

Associate Professor, University of Minnesota School of Medicine

LOCAL
INFLAMMATION

Physiological features1-3

  • Mucus hypersecretion
  • Epithelial barrier dysfunction

Associated clinical features

  • Impaired olfactory function7
  • Tissue remodeling9
  • Polyp growth and recurrence10,11

SYSTEMIC
INFLAMMATION1-3

  • Elevated IgE levels
  • Elevated eosinophil levels

*The mechanism of dupilumab action has not been definitively established.1

DUPIXENT IS THE FIRST AND ONLY FDA-APPROVED DUAL
INHIBITOR OF IL-4 AND IL-13 SIGNALING1,*

The IL-4 and IL-13 cytokines induce inflammatory responses and cell signaling, contributing to1-3:

B-cell class switching and production of IgE

Mast cell activation

Epithelial barrier dysfunction, goblet cell hyperplasia, and mucus hypersecretion

Eosinophil activation and trafficking into tissues

Play the Mechanism of Action Video to See DUPIXENT in Action

DUPIXENT is indicated as an add-on maintenance treatment in adult and pediatric patients aged 12 years and older with inadequately controlled chronic rhinosinusitis with nasal polyps, or CRS with NP.

CRS with NP is predominantly characterized by type 2 inflammation of the nose and paranasal sinuses and is frequently associated with comorbidities.

IL-4 and IL-13 are type 2 cytokines that play key roles in CRS with NP, including Th2 cell differentiation, eosinophil trafficking, and B-cell switching to IgE release.

DUPIXENT is the first and only dual inhibitor of IL-4 and IL-13 signaling addressing type 2 inflammation that contributes to CRS with NP. The mechanism of dupilumab action has not been definitively established.

In the inflammatory process, IL-4 binds to the IL-4 receptor alpha subunit at the type 1 receptor, and IL-13 binds to the IL-13 receptor alpha 1 subunit at the type 2 receptor. IL-4 can also bind to the IL-4 receptor alpha subunit at the type 2 receptor, and each interaction transmits its own signal downstream. DUPIXENT binds to IL-4 receptor alpha subunit, blocking IL-4 and IL-13 intracellular signaling. This results in reduced expression of pro-inflammatory cytokines, ultimately leading to decreased total and specific IgE. In addition, there is an impact on eosinophil activation and trafficking, along with other mechanisms that decrease type 2 inflammation. DUPIXENT is the first and only dual inhibitor of IL-4 and IL-13 signaling, two cytokines that contribute to underlying type 2 inflammation in CRS with NP.

Important Safety
Information and Indication

CONTRAINDICATION: DUPIXENT is contraindicated in patients with known hypersensitivity to dupilumab or any of its excipients.

WARNINGS AND PRECAUTIONS

Hypersensitivity: Hypersensitivity reactions, including anaphylaxis, serum sickness or serum sickness-like reactions, angioedema, generalized urticaria, rash, erythema nodosum, and erythema multiforme have been reported. If a clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue DUPIXENT.

Conjunctivitis and Keratitis: Conjunctivitis occurred more frequently in adult subjects with CRSwNP who received DUPIXENT compared to those who received placebo. Conjunctivitis and keratitis have been reported with DUPIXENT in post-marketing settings, with some patients reporting visual disturbances (e.g. blurred vision). Advise patients or their caregivers to report new-onset or worsening eye symptoms. Consider ophthalmological examination for patients who develop conjunctivitis that does not resolve following standard treatment or signs and symptoms suggestive of keratitis, as appropriate.

Eosinophilic Conditions: Patients being treated for asthma may present with clinical features of eosinophilic pneumonia or eosinophilic granulomatosis with polyangiitis (EGPA). These events may be associated with the reduction of oral corticosteroid therapy. Healthcare providers should be alert to vasculitic rash, worsening pulmonary symptoms, cardiac complications, kidney injury, and/or neuropathy presenting in their patients with eosinophilia. Cases of eosinophilic pneumonia were reported in adults who participated in the asthma development program and cases of EGPA have been reported with DUPIXENT in adults who participated in the asthma development program as well as in adults with co-morbid asthma in the CRSwNP development program. Advise patients to report signs of eosinophilic pneumonia and EGPA. Consider withholding DUPIXENT if eosinophilic pneumonia or EGPA are suspected.

Risk Associated with Abrupt Reduction of Corticosteroid Dosage: Do not discontinue systemic, topical, or inhaled corticosteroids abruptly upon initiation of DUPIXENT. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a healthcare provider. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Patients with Co-morbid Asthma: Advise patients with co-morbid asthma not to adjust or stop their asthma treatments without consultation with their physicians.

Arthralgia and Psoriatic Arthritis: Arthralgia has been reported with use of DUPIXENT with some patients reporting gait disturbances or decreased mobility associated with joint symptoms; some cases resulted in hospitalization. Cases of new-onset psoriatic arthritis requiring systemic treatment have been reported with the use of DUPIXENT. Advise patients to report new-onset or worsening joint symptoms. If the symptoms persist or worsen, consider rheumatological evaluation and/or discontinuation of DUPIXENT.

Parasitic (Helminth) Infections: It is unknown if DUPIXENT will influence the immune response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with DUPIXENT. If patients become infected while receiving treatment with DUPIXENT and do not respond to anti-helminth treatment, discontinue treatment with DUPIXENT until the infection resolves.

Vaccinations: Consider completing all age-appropriate vaccinations as recommended by current immunization guidelines prior to initiating DUPIXENT. Avoid use of live vaccines during treatment with DUPIXENT.

ADVERSE REACTIONS:

The most common adverse reactions (incidence ≥1%) in adult patients with CRSwNP are injection site reactions, eosinophilia, insomnia, toothache, gastritis, arthralgia, and conjunctivitis.

USE IN SPECIFIC POPULATIONS

  • Pregnancy: A pregnancy exposure registry monitors pregnancy outcomes in women exposed to DUPIXENT during pregnancy. Available data from case reports and case series with DUPIXENT use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Human IgG antibodies are known to cross the placental barrier; therefore, DUPIXENT may be transmitted from the mother to the developing fetus.
  • Lactation: There are no data on the presence of DUPIXENT in human milk, the effects on the breastfed infant, or the effects on milk production. Maternal IgG is known to be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for DUPIXENT and any potential adverse effects on the breastfed child from DUPIXENT or from the underlying maternal condition.

Please see accompanying full Prescribing Information.

Indication

DUPIXENT is indicated as an add-on maintenance treatment in adult and pediatric patients aged 12 years and older with inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP).

CRSwNP, chronic rhinosinusitis with nasal polyps.

Frequently Asked Questions About CRSwNP

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Eligible CRSwNP Patients
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